Weight Loss Medications

Which weight loss drug is most effective


The obesity epidemic has reached concerning levels around the world. According to the CDC, obesity affects over 40% of adults and nearly 20% of youth in the United States. This chronic condition is associated with many serious health risks including heart disease, stroke, type 2 diabetes, and certain types of cancer. With diet and exercise alone being ineffective for many people, safe and effective weight loss drugs are needed.

The history of weight loss drugs has been complex, with some having serious side effects leading to their discontinuation. In the 1930s, the first amphetamines were used for weight loss but resulted in addiction. In the 1990s, fenfluramine and dexfenfluramine were popular but ended up causing heart valve damage. The first drugs approved specifically for long-term weight loss were orlistat in 1999 and lorcaserin in 2012. Today we have several additional FDA-approved options, as well as an array of over-the-counter and off-label weight loss supplements of varying efficacy and safety.

How Weight Loss Drugs Work

Weight loss drugs affect the body in different ways to help reduce appetite, increase metabolism, or limit the absorption of calories and nutrients. Here are some of the main mechanisms:

Appetite Suppression

  • Works by affecting brain chemicals to reduce appetite and cravings. This can help limit calorie intake.
  • Pros: One of the most direct ways to support weight loss. Can significantly reduce appetite.
  • Cons: May cause side effects like headache, dizziness, fatigue, nausea. Effects wear off over time.

Increased Metabolism

  • Boosts the body’s energy expenditure and fat burning processes. Allows the body to burn more calories.
  • Pros: Increases passive calorie burning throughout the day without extra effort.
  • Cons: Can elevate heart rate and blood pressure. Effects can diminish over time.

Reduced Nutrient Absorption

  • Limits the absorption of fat, carbohydrates, and other nutrients from food.
  • Pros: Can significantly reduce the calories absorbed from meals.
  • Cons: May cause digestive issues like gas, bloating, loose stools. Doesn’t address hunger or fullness.

Appetite Suppressant and Absorption Blocker Combinations

  • Uses multiple mechanisms for enhanced effects.
  • Pros: Combines appetite and calorie absorption reduction. Can boost results.
  • Cons: More likely to cause adverse side effects with combined mechanisms.

The different mechanisms have advantages and disadvantages. Multi-component drugs aim to provide greater total impact on weight loss. Lifestyle changes are still important for long-term success.

FDA-Approved Weight Loss Drugs

While over-the-counter supplements for weight loss are readily available, there are only a few prescription medications that are FDA-approved for long-term weight management. These are regulated drugs that have undergone extensive testing in clinical trials to determine their safety and efficacy.

Some of the FDA-approved weight loss drugs include:

  • Orlistat (Xenical, Alli) – Orlistat works by blocking the absorption of dietary fats. Studies have shown it can help people lose 5-10% of their body weight over a year. Side effects include stomach pain, gas, and oily stools.

  • Liraglutide (Saxenda) – Liraglutide mimics the appetite-reducing hormone GLP-1. Clinical trials found people lost 5-10% of their weight over a year. Common side effects are nausea, diarrhea, and constipation.

  • Phentermine-topiramate (Qsymia) – This combination drug suppresses appetite and makes people feel full sooner. People lost around 10% of their weight in trials. Potential side effects include tingling, dizziness, changes in taste, and insomnia.

  • Naltrexone-bupropion (Contrave) – Contrave acts on appetite-regulating pathways in the brain. Studies showed 4-8% weight loss compared to placebo. Potential side effects can consist of nausea, constipation, headache, and dizziness.

  • Semaglutide (Wegovy) – Semaglutide is a newer GLP-1 drug approved in 2021. Clinical trials found 14-15% weight loss after 68 weeks compared to 2-3% with placebo. Frequent adverse effects include nausea, diarrhea, vomiting, and constipation.

The FDA monitors these medications closely. People considering weight loss drugs should discuss risks and realistic expectations with their doctor. Lifestyle modifications are still required for long-term success.

Off-Label and OTC Weight Loss Supplements

The supplement industry is booming, with an array of pills, powders, and herbs marketed for weight loss. These products are not regulated by the FDA and their efficacy claims are often not backed by scientific research.

Some common supplements touted for weight loss include:

  • Green tea extract: Some studies suggest EGCG, the active compound in green tea, may have a small impact on metabolism but overall the evidence for meaningful weight loss is weak.

  • Glucomannan: This soluble fiber supplement has shown mild benefits for weight loss in some studies when taken before meals. However, the weight loss effects tend to be modest.

  • Garcinia cambogia: Derived from a fruit rind, garcinia cambogia became hugely popular after Dr. Oz promoted it. But most studies show it does not lead to significant long-term weight loss.

  • Raspberry ketones: Animal studies hint at fat-burning effects and increased norepinephrine release, but human studies are lacking. There is little evidence raspberry ketones aid weight loss.

  • Meratrim: This herbal supplement combines Sphaeranthus indicus and Garcinia mangostana. Limited research suggests it may reduce body weight and hip and waist circumference compared to placebo. But larger scale studies are needed.

  • Chitosan: Some studies indicate this dietary fiber made from shellfish exoskeleton may bind to fat in the digestive tract, preventing absorption. But reviews conclude weight loss from chitosan is minimal.

Without regulation, the ingredients, purity, and dosing of supplements can vary widely between brands. Weight loss claims for supplements often rely on limited evidence. Consulting a doctor before taking supplements for weight loss is advised.

Criteria for Evaluating Effectiveness

When looking at different weight loss drugs, there are several key criteria to evaluate in determining how effective they are:

  • Amount of weight loss – The more weight that can be lost while taking the drug as directed, the more effective it generally is. Typical weight loss amounts range from 5-10% of initial body weight for approved prescription medications. Significant weight loss is considered 5% or more of total body weight.

  • Sustainability – Being able to keep the weight off long-term once stopping the medication is important. Some weight loss drugs lead to weight regain after discontinuation due to changes in hormones and metabolism. The most effective medications enable patients to more easily sustain weight loss through lifestyle changes.

  • Side effects – The frequency and severity of side effects are important in evaluating safety and tolerability. Side effects like gastrointestinal issues, headaches, and heart palpitations can impact adherence. The most effective weight loss drugs have relatively mild side effects that go away with time.

  • Cost – Weight loss medications range in cost from $30-$300+ per month depending on whether they are generic, preferred brand, or non-preferred brand drugs. Generally the most expensive drugs are newer. The cost of the drug should be evaluated relative to the amount of expected weight loss. Less expensive generics can sometimes lead to similar weight loss.

Evaluating these key criteria can help determine which weight loss drug may be most effective for an individual’s circumstances and health status. Sustainable, significant weight loss with mild side effects at a reasonable cost provide a good indicator of effectiveness.

The Most Effective Clinically-Tested Drugs

When evaluating weight loss drugs for effectiveness, it’s important to look at those that have been rigorously tested in clinical trials and shown to produce significant weight loss compared to a placebo. Based on the available clinical evidence, two prescription drugs stand out as the most effective for weight loss:


Phentermine is an appetite suppressant that has been prescribed for weight loss since the 1950s. It is the most commonly prescribed weight loss medication in the United States. Numerous clinical trials have shown that phentermine can produce significant weight loss of around 5-10% of body weight over 3-6 months.

In a meta-analysis of 6 studies with over 2,100 participants, those taking phentermine lost an average of 6.3% more weight than those taking a placebo over 12-52 weeks. There are few side effects, mainly consisting of increased heart rate and elevated blood pressure. Phentermine appears to be most effective when combined with lifestyle modifications.


Liraglutide is a newer drug approved by the FDA in 2014 for chronic weight management. It mimics a hormone called GLP-1 that regulates appetite and food intake. Clinical trials show that liraglutide can lead to average weight loss of 5-10%, better than other diabetes medications.

In a 56-week study of over 3,300 overweight or obese participants, those taking liraglutide lost an average of 8% of their body weight, compared to 2.6% for placebo. Common side effects are nausea, diarrhea, and vomiting. Liraglutide requires daily injection, which some people may dislike. But it has the advantage of also treating type 2 diabetes.

So in summary, phentermine and liraglutide have the strongest clinical evidence backing their effectiveness for weight loss when combined with lifestyle modifications. But medications should not replace improved nutrition and increased physical activity, which provide the foundation for long-term weight management.

Lifestyle Changes That Optimize Results

When used properly, prescription weight loss drugs can help jumpstart your journey toward a healthier weight. However, they work best when combined with lifestyle changes like diet, exercise, and behavior modification techniques.


  • Focus on a balanced, reduced-calorie diet full of fiber, protein, and healthy fats to help manage hunger and promote weight loss.
  • Reduce intake of processed foods, added sugars, and refined carbs. Prioritize whole foods, fruits, vegetables, lean proteins, nuts, seeds, and whole grains.
  • Watch portion sizes and calorie density. Fill up on low-calorie foods with high volume.
  • Stay hydrated by drinking water instead of sugary drinks.


  • Aim for 150-300 minutes of moderate aerobic exercise per week, plus 2 strength training sessions.
  • Gradually increase your level of activity starting out modestly. Go for walks, swim, cycle, or do other activities you enjoy.
  • Being active helps burn calories and build metabolism-boosting muscle.

Behavior Modification

  • Set realistic weight loss goals of 1-2 lbs per week for steady, sustainable progress.
  • Use tools like food journals, apps, and calendars to track progress.
  • Identify triggers and patterns related to overeating. Break unhealthy habits and cycles.
  • Get support from professionals, friends, or groups. Having accountability helps motivation.
  • Make permanent lifestyle adjustments rather than temporary quick fixes for long-term success.

Following a healthy lifestyle optimizes your ability to lose weight and keeps it off. Prescription weight loss medications work best when paired with these types of changes.

Special Considerations

When evaluating weight loss drugs for effectiveness, it’s important to consider how they may affect different demographics and populations. The same drug can produce varied results in different people based on factors like age, gender, ethnicity, and health status.

For example, some weight loss drugs may be more effective for younger patients compared to older ones. Women may experience different effects than men. People with certain medical conditions or taking other medications need to be especially cautious when using weight loss drugs due to potential interactions. Ethnicity can also play a role, as genetics influence how medications are metabolized.

Long-term safety is another key consideration when determining effectiveness. Some side effects or health risks may only emerge after taking a weight loss drug for many months or years. It’s important to monitor long-term clinical trial data and post-marketing surveillance to catch any delayed adverse effects. Short-term studies may not reveal the full safety profile.

The Future of Weight Loss Drugs

The future of pharmaceutical weight loss drugs is likely to focus on new drug targets and mechanisms that may enable greater efficacy and safety. Research is exploring pathways beyond suppressing appetite and increasing metabolism, like altering gut bacteria and modulating hormones that regulate hunger and fat storage.

New weight loss medications introduced in the future will likely remain prescription-only due to the risks inherent in these drugs. Any medication that substantially alters metabolism, appetite, or nutritional absorption carries risks and requires medical supervision. However, some new over-the-counter supplements may emerge that take a gentler approach, like providing probiotics to improve gut health.

There are ethical considerations around developing new weight loss drugs as well. As society struggles with rising obesity rates, there is pressure to find medical solutions. However, we must balance this need with ensuring drugs are safe over the long-term and not overused or abused. Pharmaceutical companies have a responsibility to avoid predatory marketing and ensure drugs are prescribed appropriately to patients who have first tried lifestyle modifications. We must also work to reduce weight stigma and avoid positioning medication as a quick fix or the sole solution.

Overall, expect to see continuing pharmaceutical research and breakthroughs focused on the biology of weight regulation. While new medications hold promise, long-term data on safety and outcomes will be critical. A holistic approach is still key, with nutrition, exercise and behavioral changes providing the foundation for healthy and sustainable weight loss over time.


When evaluating weight loss drugs, it’s important to look at long-term results and safety in addition to short-term efficacy. Based on clinical trial data, the most effective FDA-approved prescription weight loss medications seem to be phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), and semaglutide (Wegovy). However, even the best weight loss drugs result in fairly modest weight loss compared to placebo groups in studies.

For consumers, it’s key to have realistic expectations about weight loss drugs. While they may help you lose 5-15% more weight compared to diet and exercise alone, they are not a magic bullet. The most effective and sustainable weight loss plans combine prescription medications (if appropriate) with lifestyle changes like improved nutrition, more physical activity, stress management, and better sleep habits. Weight loss takes time and commitment, but prescription medications can serve as a helpful supporting tool when used properly under medical supervision.

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